Integration of structural dynamics and molecular evolution via protein interaction networks: A new era in genomic medicine

Avishek Kumar, Brandon M. Butler, Sudhir Kumar, S. Banu Ozkan

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Sequencing technologies are revealing many new non-synonymous single nucleotide variants (nsSNVs) in each personal exome. To assess their functional impacts, comparative genomics is frequently employed to predict if they are benign or not. However, evolutionary analysis alone is insufficient, because it misdiagnoses many disease-associated nsSNVs, such as those at positions involved in protein interfaces, and because evolutionary predictions do not provide mechanistic insights into functional change or loss. Structural analyses can aid in overcoming both of these problems by incorporating conformational dynamics and allostery in nSNV diagnosis. Finally, protein-protein interaction networks using systems-level methodologies shed light onto disease etiology and pathogenesis. Bridging these network approaches with structurally resolved protein interactions and dynamics will advance genomic medicine.

Original languageEnglish (US)
JournalCurrent Opinion in Structural Biology
DOIs
StateAccepted/In press - 2015

Fingerprint

Protein Interaction Maps
Molecular Evolution
Medicine
Nucleotides
Exome
Proteins
Genomics
Diagnostic Errors
Technology

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

@article{38ef6260fedc46b2b02485197b7e8d60,
title = "Integration of structural dynamics and molecular evolution via protein interaction networks: A new era in genomic medicine",
abstract = "Sequencing technologies are revealing many new non-synonymous single nucleotide variants (nsSNVs) in each personal exome. To assess their functional impacts, comparative genomics is frequently employed to predict if they are benign or not. However, evolutionary analysis alone is insufficient, because it misdiagnoses many disease-associated nsSNVs, such as those at positions involved in protein interfaces, and because evolutionary predictions do not provide mechanistic insights into functional change or loss. Structural analyses can aid in overcoming both of these problems by incorporating conformational dynamics and allostery in nSNV diagnosis. Finally, protein-protein interaction networks using systems-level methodologies shed light onto disease etiology and pathogenesis. Bridging these network approaches with structurally resolved protein interactions and dynamics will advance genomic medicine.",
author = "Avishek Kumar and Butler, {Brandon M.} and Sudhir Kumar and Ozkan, {S. Banu}",
year = "2015",
doi = "10.1016/j.sbi.2015.11.002",
language = "English (US)",
journal = "Current Opinion in Structural Biology",
issn = "0959-440X",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Integration of structural dynamics and molecular evolution via protein interaction networks

T2 - A new era in genomic medicine

AU - Kumar, Avishek

AU - Butler, Brandon M.

AU - Kumar, Sudhir

AU - Ozkan, S. Banu

PY - 2015

Y1 - 2015

N2 - Sequencing technologies are revealing many new non-synonymous single nucleotide variants (nsSNVs) in each personal exome. To assess their functional impacts, comparative genomics is frequently employed to predict if they are benign or not. However, evolutionary analysis alone is insufficient, because it misdiagnoses many disease-associated nsSNVs, such as those at positions involved in protein interfaces, and because evolutionary predictions do not provide mechanistic insights into functional change or loss. Structural analyses can aid in overcoming both of these problems by incorporating conformational dynamics and allostery in nSNV diagnosis. Finally, protein-protein interaction networks using systems-level methodologies shed light onto disease etiology and pathogenesis. Bridging these network approaches with structurally resolved protein interactions and dynamics will advance genomic medicine.

AB - Sequencing technologies are revealing many new non-synonymous single nucleotide variants (nsSNVs) in each personal exome. To assess their functional impacts, comparative genomics is frequently employed to predict if they are benign or not. However, evolutionary analysis alone is insufficient, because it misdiagnoses many disease-associated nsSNVs, such as those at positions involved in protein interfaces, and because evolutionary predictions do not provide mechanistic insights into functional change or loss. Structural analyses can aid in overcoming both of these problems by incorporating conformational dynamics and allostery in nSNV diagnosis. Finally, protein-protein interaction networks using systems-level methodologies shed light onto disease etiology and pathogenesis. Bridging these network approaches with structurally resolved protein interactions and dynamics will advance genomic medicine.

UR - http://www.scopus.com/inward/record.url?scp=84949653793&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84949653793&partnerID=8YFLogxK

U2 - 10.1016/j.sbi.2015.11.002

DO - 10.1016/j.sbi.2015.11.002

M3 - Article

C2 - 26684487

AN - SCOPUS:84952720717

JO - Current Opinion in Structural Biology

JF - Current Opinion in Structural Biology

SN - 0959-440X

ER -